As­traZeneca’s big MYS­TIC tri­al ends a com­plete fail­ure as Imfinzi/treme­li­mum­ab com­bo flops on over­all sur­vival

Last year, As­traZeneca preached pa­tience af­ter ini­tial da­ta showed its check­point in­hibitor Imfinzi com­bined with their in-house CT­LA-4 drug failed to meet the pri­ma­ry end­point of pro­gres­sion-free sur­vival in a piv­otal lung can­cer tri­al. On Fri­day, that faith proved in vain as the im­munother­a­py al­so failed to im­prove over­all sur­vival in the keen­ly watched MYS­TIC tri­al.

The tri­al test­ed Imfinzi both as a monother­a­py and in com­bi­na­tion with an­oth­er check­point in­hibitor, treme­li­mum­ab, against chemother­a­py in treat­ment-naive pa­tients with stage IV non-small cell lung can­cer (NSCLC), a cru­cial are­na in the bat­tle for check­point drug dom­i­nance.

The phar­ma gi­ant $AZN con­ced­ed Fri­day morn­ing that the com­bi­na­tion — once con­sid­ered a cor­ner­stone of As­traZeneca’s check­point de­vel­op­ment strat­e­gy — ac­tu­al­ly per­formed worse than Imfinzi alone for the over­all sur­vival end­point, with a haz­ard ra­tio of 0.76 for the so­lo drug com­pared to an ane­mic 0.85 for the two to­geth­er.

Sean Bo­hen

While As­traZeneca’s pipeline has of­ten come up short, there have been a string of ma­jor suc­cess­es in on­col­o­gy for the com­pa­ny. This tri­al was con­sid­ered crit­i­cal in putting the brakes on the blitz­ing gains Mer­ck $MRK and Bris­tol-My­ers Squibb have made af­ter es­tab­lish­ing their lead in the lu­cra­tive front­line can­cer field. The study was al­so tout­ed by CEO Pas­cal So­ri­ot as an in­di­ca­tor of the British drug­mak­er’s val­ue as an in­de­pen­dent en­ti­ty, when it spurned Pfiz­er’s $PFE $118 bil­lion takeover bid in 2014

In a state­ment on Fri­day, As­traZeneca al­so sug­gest­ed that al­though sta­tis­ti­cal sig­nif­i­cance for over­all sur­vival had not been met, the da­ta mer­it­ed fur­ther analy­sis in ex­plorato­ry sub­groups. That’s not like­ly go­ing to in­spire much en­thu­si­asm.

Brad Lon­car

In MYS­TIC, “CT­LA-4 tru­ly of­fered no ben­e­fit or sig­nal at all”, said Brad Lon­car, man­ag­er of the Lon­car Can­cer Im­munother­a­py ETF. “I would think hard about these re­sults if I was one of the com­pa­nies out there de­vel­op­ing me-too or me-bet­ter CT­LA-4s (of which there are many). Giv­en its tox­i­c­i­ty pro­file and now the emerg­ing com­bo ef­fi­ca­cy we are see­ing in some of these can­cers out­side of melanoma, its win­dow is look­ing quite nar­row.”

As­traZeneca’s shares were al­so un­der pres­sure again on the fail­ure. Its stock is down more than 3% in pre-mar­ket trad­ing. Shares fell sharply last year on the PFS miss, evap­o­rat­ing some $14 bil­lion off the com­pa­ny’s val­ue.

Since that ini­tial set­back on MYS­TIC, though, As­traZeneca scored a big win with its PA­CIF­IC tri­al for Imfinzi, win­ning a sig­nif­i­cant mar­ket niche for it­self in stage III NSCLC. But the fail­ure here will sting, nev­er­the­less.

Chief med­ical of­fi­cer Sean Bo­hen spot­light­ed the suc­cess on the monother­a­py side, but con­ced­ed the key fail­ure:

We are en­cour­aged to see that Imfinzi monother­a­py ac­tiv­i­ty is in-line with that of the an­ti-PD-1 class in pre­vi­ous­ly-un­treat­ed pa­tients with Stage IV non-small cell lung can­cer; how­ev­er, we are dis­ap­point­ed that these re­sults missed sta­tis­ti­cal sig­nif­i­cance. We re­main con­fi­dent in Imfinzi as the cor­ner­stone of our IO pro­gramme and con­tin­ue to eval­u­ate its po­ten­tial in on­go­ing non-small cell lung can­cer tri­als, in­clud­ing Imfinzi and Imfinzi plus treme­li­mum­ab in com­bi­na­tion with chemother­a­py.


Im­age: Pas­cal So­ri­ot. AP IM­AGES

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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Am­gen aug­ments Asia foothold by tak­ing over Astel­las joint ven­ture in Japan

California-based Amgen, which does the bulk of its business in the United States, made its ambition to reinvigorate its growth prospects by expanding its presence in Asia clear at the sidelines of the JP Morgan healthcare conference in San Francisco earlier this month.

The Thousand Oaks-based company on Thursday executed its plan to dissolve the joint venture with Astellas — created in 2013 — to operate the unit independently in Japan. With its rapidly aging population, the region represents an appealing market for Amgen’s osteoporosis treatments Prolia and Evenity as well as a cholesterol-lowering injection Repatha.

Daphne Zohar (PureTech)

PureTech bags $200M from sale of Karuna shares — still siz­zling from promis­ing schiz­o­phre­nia da­ta

Cashing in on the exuberance around Karuna Therapeutics and its potential blockbuster CNS drug, PureTech has sold a chunk of the biotech’s shares to Goldman Sachs for $200 million.

Boston-based PureTech had helped Eli Lilly vet Steve Paul launch Karuna and invent its lead program, which combines two old drugs that both act on the muscarinic receptor and balances each other out. Xanomeline, a discard from Lilly, stimulates the M1 and M4 receptors; trospium is an muscarinic receptor antagonist approved to treat overactive bladders.

UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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Roche cracks Chi­na's ADC mar­ket open as Kad­cy­la scores its first breast can­cer OK in the coun­try

Roche’s Kadcyla has become the first antibody-drug conjugate to enter the Chinese market, marking a dramatic advance for both the Swiss pharma giant and the therapeutic class.

The local arm of Roche announced the approval late Tuesday, which covers the therapy’s use in the adjuvant setting in patients with early HER-2 positive breast cancer who still have residual invasive disease after receiving paclitaxel and Herceptin as neoadjuvant treatment.

Wuhan virus out­break trig­gers in­evitable small-biotech ral­ly

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.